Fig. 8: Neuroinflammatory cytokine signatures reveal myeloid cell regulation in MS across CNS compartments.
From: In vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation
a, UMAP of human CSF monocyte/macrophages across datasets after integration. b, Pseudobulked average expression per individual of the neuroinflammatory cytokine signatures across human MS CSF datasets and disease stages, and a control CSF dataset from MCI/AD. N = 5 idiopathic intracranial hypertension (IIH), 6 radiologically isolated syndrome (RIS) and 14 individuals with MS, n = 5 individuals with IIH and 5 individuals with MS from ref. 32, n = 45 healthy individuals and 14 individuals with MCI/AD from ref. 33. c, UMAP of human microglia from ref. 35. IRM, interferon-responsive microglia; DAM, disease-associated microglia. d, Pseudobulked average expression per individual of the neuroinflammatory cytokine signatures in microglia derived from gray matter of control individuals or people with MS or MCI/AD. N = 12 samples for control gray matter (GM), 15 for normal-appearing gray matter (NAGM) in MS and 13 for gray matter lesion (GML) in MS, n = 13 healthy individuals, 8 individuals with MCI and 20 individuals with AD from ref. 36. e, Density distribution of microglial clusters across white matter lesion types in human MS. WM, control white matter; NAWM, normal-appearing white matter; AL, active lesion; CAL, chronic active lesion; CIL, chronic inactive lesion; RL, remyelinating lesion. f, Pseudobulked average expression per individual of the neuroinflammatory cytokine signatures across microglial clusters in the white matter. Respectively, n = 36, 23, 19, 30 and 18 samples in homeostatic to MHC class II-recovery clusters. b, One-way ANOVA, IFNγ F = 4.9165, P = 0.0171, TNF F = 0.7544, P = 0.4821, GM-CSF F = 0.2334, P = 0.7938, TGFβ F = 0.727, P = 0.5088, followed by two-tailed t-tests or Wilcoxon tests comparing RIS/MS/MCI-AD to their dataset control (IIH or healthy); d, One-way ANOVA IFNγ F = 2.0908, P = 0.1379, TNF F = 0.2422, P = 0.7861, GM-CSF F = 2.0325, P = 0.1454, TGFβ F = 1.5998, P = 0.2156, followed by two-tailed t-tests NAGM and GML to healthy GM for ref. 35 MS data; IFNγ F = 1.803, P = 0.168, TNF F = 1.1469, P = 0.3284, GM-CSF F = 6.0476, P = 0.0052, TGFβ F = 0.7814, P = 0.465, followed by two-tailed t-tests comparing MCI/AD to healthy for ref. 36 MCI/AD data; f, one-way ANOVA TNF F = 2.3413, P = 0.0588, Kruskal–Wallis test IFNγ P = 0.0039, GM-CSF P < 0.0001, TGFβ P < 0.0001, followed by two-tailed t-tests or Wilcoxon tests comparing all clusters to the homeostatic cluster, adjusting the P values by the FDR method; In the box plots, the line shows median, the box extends from Q1 to Q3, and the whiskers extend to the smallest and largest values within 1.5 times the interquartile range from Q1 and Q3. NS, P value > 0.1, P value shown if 0.05 < P < 0.1, *P value < 0.05, **P value < 0.01, ***P value < 0.001, ****P value < 0.0001.
